IgG subclass switch capacity is low in switched and in IgM-only, but high in IgD+IgM+, post-germinal center (CD27+) human B cells. 2001

C Werner-Favre, and F Bovia, and P Schneider, and N Holler, and M Barnet, and V Kindler, and J Tschopp, and R H Zubler
Division of Hematology, Department of Medicine, Geneva University Hospital, Geneva, Switzerland.

Recent studies have shown that in humans the germinal center reactions produce three types of V(D)J mutated B cells in similar proportions, i.e. Ig-switched, IgD-IgM+ (IgM-only) and IgD+IgM+ cells, and that together they form the CD27+ compartment of recirculating B cells. We investigated the Ig isotype switch capacity of these cells. Peripheral blood B subsets were sorted and IgG subclass secretion in presence or absence of IL-4 was compared in B cell assays which lead to Ig secretion in all (coculture with EL-4 thymoma cells) or only in CD27+ (CD40L stimulation) B cells. Already switched IgG+ B cells showed no significant sequential switch and IgM-only cells also had a low switch capacity, but IgD+CD27+ switched as much as IgD+CD27- B cells to all IgG subclasses. Thus, in switched B cells some alterations compromising further switch options occur frequently; IgM-only cells may result from aborted switch. However, IgD+CD27+ human B cells, extensively V(D)J mutated and "naive" regarding switch, build up a repertoire of B cells combining (1) novel cross-reactive specificities, (2) increased differentiation capacity (including after T-independent stimulation by Staphylococcus aureus Cowan I) and (3) the capacity to produce appropriate isotypes when they respond to novel pathogens.

UI MeSH Term Description Entries
D007072 Immunoglobulin D An immunoglobulin which accounts for less than 1% of plasma immunoglobulin. It is found on the membrane of many circulating B LYMPHOCYTES. IgD,IgD1,IgD2
D007074 Immunoglobulin G The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B. Gamma Globulin, 7S,IgG,IgG Antibody,Allerglobuline,IgG(T),IgG1,IgG2,IgG2A,IgG2B,IgG3,IgG4,Immunoglobulin GT,Polyglobin,7S Gamma Globulin,Antibody, IgG,GT, Immunoglobulin
D007075 Immunoglobulin M A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally was called a macroglobulin. Gamma Globulin, 19S,IgM,IgM Antibody,IgM1,IgM2,19S Gamma Globulin,Antibody, IgM
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016175 B-Lymphocyte Subsets A classification of B-lymphocytes based on structurally or functionally different populations of cells. B-Cell Subsets,Tumor-Infiltrating B Cells,Tumor-Infiltrating B Lymphocytes,B Effector 1 Cells,B Effector 2 Cells,B-1 Cells,B-1 Lymphocytes,B-2 Lymphocytes,B-Lymphocytes, Effector,B1 Lymphocytes,B2 Lymphocytes,Be1 Cells,Be2 Cells,Effector B Cells,B 1 Cells,B 1 Lymphocytes,B 2 Lymphocytes,B Cell Subsets,B Cell, Tumor-Infiltrating,B Lymphocyte Subsets,B Lymphocyte, Tumor-Infiltrating,B-1 Cell,B-1 Lymphocyte,B-2 Lymphocyte,B-Cell Subset,B-Lymphocyte Subset,B-Lymphocyte, Effector,B1 Lymphocyte,B2 Lymphocyte,Be1 Cell,Be2 Cell,Cell, B-1,Cell, Be1,Cell, Be2,Effector B Cell,Effector B-Lymphocyte,Effector B-Lymphocytes,Lymphocyte, B-1,Lymphocyte, B-2,Lymphocyte, B1,Lymphocyte, B2,Tumor Infiltrating B Cells,Tumor Infiltrating B Lymphocytes,Tumor-Infiltrating B Cell,Tumor-Infiltrating B Lymphocyte
D017578 Immunoglobulin Class Switching Gene rearrangement of the B-lymphocyte which results in a substitution in the type of heavy-chain constant region that is expressed. This allows the effector response to change while the antigen binding specificity (variable region) remains the same. The majority of class switching occurs by a DNA recombination event but it also can take place at the level of RNA processing. Class Switching,Ig Class Switching,Isotype Switching,Class Switching, Ig,Class Switching, Immunoglobulin,Class Switchings,Class Switchings, Ig,Class Switchings, Immunoglobulin,Ig Class Switchings,Immunoglobulin Class Switchings,Isotype Switchings,Switching, Class,Switching, Ig Class,Switching, Immunoglobulin Class,Switching, Isotype,Switchings, Class,Switchings, Ig Class,Switchings, Immunoglobulin Class,Switchings, Isotype
D018127 Tumor Necrosis Factor Receptor Superfamily, Member 7 A member of the tumor necrosis factor receptor superfamily found on most T-LYMPHOCYTES. Activation of the receptor by CD70 ANTIGEN results in the increased proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS. Antigens, CD27,CD27 Antigens,T-Cell Activation Antigen,Antigen, CD27,TNFRSF7 Receptor,Activation Antigen, T-Cell,Antigen, T-Cell Activation,CD27 Antigen,Receptor, TNFRSF7,T Cell Activation Antigen
D018858 Germinal Center The activated center of a lymphoid follicle in secondary lymphoid tissue where B-LYMPHOCYTES are stimulated by antigens and helper T cells (T-LYMPHOCYTES, HELPER-INDUCER) are stimulated to generate memory cells. Center, Germinal,Centers, Germinal,Germinal Centers

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